In a Phase I study, patients with epithelial malignancies are being treated with two cytotoxic agents that bind to the LeY antigen. One is a single chain immunotoxin LMB-7 (B3(Fv)PE38). The other is 90Y-MAb B3. Both trials should end in 1997. Because LMB-7 is unstable in human plasma, a very stable form of LMB-7 termed LMB-9 has been made in which a disulfide bond stabilizes the Fv interaction. A clinical trial with LMB-9 will begin in late 1998. In addition a disulfide stabilized immunotoxin (erb38) that binds to Her2/neu has been made and will soon be evaluated in patients with breast cancer and other Her/2neu positive malignancies. A Phase I study is also being conducted with immunotoxin LMB-2 (anti- Tac(Fv)-PE38) in patients with T cell malignancies or other malignancies that express p55, the alpha subunit of the IL2 receptor, such as Hodgkin's disease and CLL. A disulfide stabilized recombinant immunotoxin that targets CD22 expressed by malignant B cells has undergone preclinical evaluation and has been approved for a clinical trial. The immunotoxin will be produced in early 1998 for a trial to begin late in 1998. A genetically engineered fusion of IL4 with PE38 (IL4-PE38KDEL) containing a KDEL sequence at the carboxyl terminus to increase cytotoxic activity was produced and shown to be very cytotoxic to glioblastoma cell lines. A clinical lot of this chimeric toxin has been produced. It is well tolerated by rodents and monkeys and an IND was approved in 1997. Dr. Robert Rand, a neurosurgeon at the John Wayne Cancer Center has initiated a Phase I trial with this agent in patients with recurrent glioblastoma in which the chimeric toxin is slowly perfused directly into the tumor.